chr10-113565686-C-A

Variant names:

• chr10-113565686-C-A
• rs4918851
• NM_004132.5:c.70-1803C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004132.5(HABP2):​c.70-1803C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,100 control chromosomes in the GnomAD database, including 9,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9403 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 6 publications found

Genes affected

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	NM_004132.5	MANE Select	c.70-1803C>A		intron	N/A	NP_004123.1
	HABP2	NM_001177660.3		c.-9-1803C>A		intron	N/A	NP_001171131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	ENST00000351270.4	TSL:1 MANE Select	c.70-1803C>A		intron	N/A	ENSP00000277903.4
	HABP2	ENST00000542051.5	TSL:2	c.-9-1803C>A		intron	N/A	ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49491 AN: 151980 Hom.: 9375 Cov.: 33

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49570 AN: 152100 Hom.: 9403 Cov.: 33 AF XY: 0.326 AC XY: 24222 AN XY: 74372

African (AFR) AF: 0.467 AC: 19377 AN: 41462

American (AMR) AF: 0.467 AC: 7143 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2641 AN: 5170

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4814

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15603 AN: 68002

Other (OTH) AF: 0.327 AC: 690 AN: 2110

Alfa AF: 0.264 Hom.: 4351

Bravo AF: 0.361

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.73
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4918851; hg19: chr10-115325445;